COG133, an apolipoprotein E-derived mimetic peptide, has been proposed as a therapeutic candidate due to its immunomodulatory properties. Its potential role in diabetic wound healing, where impaired f Show more
COG133, an apolipoprotein E-derived mimetic peptide, has been proposed as a therapeutic candidate due to its immunomodulatory properties. Its potential role in diabetic wound healing, where impaired fibroblast function and chronic inflammation are major obstacles, remains largely unexplored. In this study, human diabetic dermal fibroblasts were treated with COG133 to evaluate its effects on cell viability, migration, and gene expression of ApoE, miR-146a, NF-κB, TRAF-6, and IL-6. In addition, the antibacterial and antibiofilm activities of COG133 were assessed against Gram-positive and Gram-negative bacteria. COG133 enhanced fibroblast migration without affecting viability, upregulated miR-146a, and reduced IL-6 and ApoE expression, while NF-κB and TRAF-6 remained unchanged. Antibacterial assays revealed inhibitory effects, with the lowest MIC against Show less
Epithelial-to-mesenchymal transition (EMT) is essential for normal development and cancer progression. However, how nuclear Lamins regulate EMT is unclear. Here, we show that Lamin A/C modulates the e Show more
Epithelial-to-mesenchymal transition (EMT) is essential for normal development and cancer progression. However, how nuclear Lamins regulate EMT is unclear. Here, we show that Lamin A/C modulates the epithelial-mesenchymal (E-M) plasticity of cells through its interaction with the chromatin organizer, EZH2. The overexpression of Lamin A reinforces an epithelial identity, while its depletion promotes a mesenchymal phenotype. This positions Lamin A/C as a crucial modulator of Epithelial-Mesenchymal plasticity. Furthermore, CDK1-mediated phosphorylation of Lamin A/C (Ser22) and EZH2 (Thr345) disrupts Lamin A/C-EZH2 interaction, destabilizing EZH2, with a concomitant decrease in the occupancy of the heterochromatin mark (H3K27me3) on the SNAI1, TWIST1, and ZEB1 promoters, thereby facilitating a transition towards mesenchymal transcriptional programs. Conversely, phosphodeficient Lamin A/C (S22A) and EZH2 (T345A) mutants restore epithelial identity, highlighting a regulatory role of the Lamin A/C-EZH2 axis in maintaining epithelial homeostasis. In vivo, xenograft assays in NOD-SCID mice reveal that while phosphorylated Lamin A/C or EZH2 promote tumor growth and metastasis, phospho-deficient mutants markedly suppress it. Lamin A/C-EZH2 interaction regulates the expression of E-M-associated transcription factors, highlighting the role of this interaction in modulating transcriptional plasticity, thereby serving as a potential therapeutic target for regulating metastasis in breast cancers. Show less